Ketek case keeps glare on reform

Critics say FDA errors underline drug peril

Feb 14, 2007 | The Star Ledger

The Food and Drug Administration's missteps in approving the controversial antibiotic Ketek were cited at a congressional hearing yesterday as further evidence of the need for major drug safety reform.

FDA whistle-blowers, medical experts and members of Congress said the FDA in 2004 approved Ketek, since linked to liver failures, despite serious safety warnings from scientific reviewers and evidence of fraudulent data.

They told the House Energy and Commerce subcommittee on oversight and investigations that scientific dissent was discouraged and muzzled inside the agency regarding Ketek, and pertinent information withheld from FDA advisory committees.

"FDA approved Ketek despite knowing that it could kill people from liver damage and that tens of millions of people would be exposed to it; despite FDA knowing that the drugmaker submitted fabricated data; and despite knowing that Ketek is no better than other antibiotics, and may not even work," said David Ross, a former FDA scientist who had been one of the lead medical reviewers for Ketek.

Ross, who raised his concerns publicly last year about the Sanofi-Aventis drug and later left the agency in frustration, said the episode is emblematic of an agency culture that favors drug approvals over safety. He said "we are certain to see more Keteks" without "significant changes in our drug safety system and FDA."

On eve of the congressional hearing, the FDA withdrew its approval for two of the three main uses for Ketek, acute bacterial sinusitis and acute chronic bronchitis.

"The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications," the FDA said.

It said the drug can remain on the market for treatment of pneumonia. Last year, the FDA changed the labeling to warn of potential liver problems, and this week added a new warning that the drug should not be used in patients with myasthenia gravis, a disease that can cause life-threatening muscle weakness.

Sanofi-Aventis maintains the drug continues to be an important treatment option. The antibiotic has been prescribed nearly six million times in the United States.

The concerns about Ketek follow other highly publicized FDA problems, including the withdrawal of the painkillers Vioxx and Bextra; the slowness in providing new warnings about the dangers of widely used antidepressants and accusations the agency is too cozy with the drug industry.

An Institute of Medicine panel recently called for an overhaul of the FDA's drug safety system, saying the agency is failing to adequately protect the public.

A number of reform proposals are pending in Congress, including creating a new drug safety center inside the FDA; mandating more disclosure of clinical trial data; giving the agency authority to order rather than negotiate new labeling changes; requiring companies to carry out post-market safety studies and prohibiting ads promoting new drugs for up to two years.

Rep. Bart Stupak (D-Mich.), the subcommittee chairman, said the evidence regarding Ketek and other cases suggests that the "FDA's ability to ensure a safe drug supply has been greatly compromised" by a rush to approve new medications.

Rep. John Dingell (D-Mich.), chairman of the full Energy and Commerce Committee, added that there has been "a fundamental breakdown in policies and procedures in evaluating the safety of drugs."

The committee heard from a number of witnesses, including John Powers, a former FDA scientist, who said "Ketek was the symptom of a much larger problem" that involves a misguided review process for new antibiotics. He said this process is driven by pressure from industry, resulting in "approval of numerous antibiotics whose effectiveness is unclear."

David Graham, the FDA scientist and whistle-blower who publicly attacked the agency for its handling of Vioxx and other drugs, said "the Ketek story is about the FDA's betrayal of the public trust."

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